Melanoma Associated Spongiform Scleropathy: Characterization, Biochemical and Immunohistochemical studies

Abstract

Summary. Melanoma associated spongiform scleropathy (MASS) is a non‐inflammatory scleral change with a spongiotic morphology seen in association with uveal melanoma. MASS is seen as whitish spindle shaped areas within the sclera that is adjacent to and in contact with a choroidal or ciliary body melanoma. This change can be seen as small scattered lesions in the inner scleral layers or as extensive areas along the whole extent of contact between the tumour and the sclera and involves most of the scleral thickness. MASS changes of different grades of severity were seen in 38% of 363 melanoma eyes investigated. The presence of MASS showed a statistical correlation with age. A significant high incidence of MASS was found in old age groups. This might due to the fact that MASS needs a longer period of contact between the tumour and the sclera to develop. It is also possible that age‐related changes of the extracellular matrix might alter its response to melanoma produced factors leading to the development of MASS. The development of MASS and its severity are influenced by the extent of contact between the tumour and the sclera. This is supported by the significant statistical relation between the largest basal diameter of the tumours and the severity of MASS. Statistical correlation was found between MASS and scleral and extrascleral tumour extension. More than 90% of 82 specimens that showed tumour extension were associated with MASS. A biochemical analysis of scleral samples taken from areas with severe MASS showed a significant reduction of the main amino acids of collagen type I, which is the main scleral collagen. The amounts of total scleral proteins were significantly reduced. This scleral protein reduction is associated with an increase in glycosaminoglycans. These findings indicate a collagen degradation process. Immunohistochemical studies were performed to investigate the expression of matrix metalloproteinases (MMPs). In situ hybridization showed a significantly more frequent and more intense expression of MMP‐2 by scleral fibroblasts in areas with MASS compared with areas without MASS. This was also seen by immunohistochemical staining. Similar high frequency and intense expression of MMP‐2 were seen in tumour infiltrating macrophages. The results of biochemical and immunohistochemical studies indicate a collagen degradation process. This degradation may be the result of the proteolytic enzyme MMP‐2 expressed by scleral fibroblasts under the effect of tumour humeral factors and/or tumour infiltrating macrophages. This scleral degradation results in fragmentation of the scleral collagen fibrils. This along with the accumulation of water in the sclera, as a result of the increase in the production of glycosaminoglycans, results in increase of scleral thickness in MASS areas and forms the histopathological picture of MASS. The scleral degradation may facilitate tumour invasion and may explain the statistical relation between MASS and scleral tumour invasion. MASS was found in a few of the eyes tha...

Melanoma-Associated Spongiform Scleropathy in Oculodermal Melanocytosis with Primary Orbital Melanoma

“…The implications of the finding in this case are unknown, as the mechanism(s) and clinical significance of melanoma-associated spongiform scleropathy are partially understood [9] . There is evidence that the collagen changes in melanoma-associated spongiform scleropathy may predispose to scleral invasion and possibly contribute to a less favorable outcome [1][2][3][4] . However, in our case, the scleral changes did not arise next to a melanoma, but rather adjacent to a large, heavily pigmented nevus, which had been present from birth (or at least at a very young age).…”

“…In the most comprehensive paper on the subject of melanoma-associated spongiform scleropathy, the scleral disorder was defined by light microscopic criteria alone using hematoxylin-eosin stains [1] . Although that report documented increased total glycosaminoglycan within the affected sclera, this was not correlated with any histochemical stain.…”

“…Subsequent studies have shown that melanoma-associated spongiform scleropathy occurs in areas of direct sclera contact with uveal melanoma. This abnormality has been reported in 11% to one third of eyes with posterior uveal melanoma [1][2][3] . Scleral aberration may have been overlooked by pathologists in the past, because the collagen alterations were attributed to fixation or processing artifact.…”

“…Scleral aberration may have been overlooked by pathologists in the past, because the collagen alterations were attributed to fixation or processing artifact. Although its pathogenesis remains obscure, preliminary evidence suggests that the degenerative change may enhance the risk of scleral invasion and extrascleral spread [1][2][3][4] . We report a patient with oculodermal melanocytosis (or nevus of Ota) who developed an ipsilateral primary orbital melanoma.…”

“…Melanoma-associated spongiform scleropathy is a noninflammatory degenerative change reported exclusively with choroidal or ciliary body melanoma [1] . The first description of this condition is attributed to Stefani at the European Ophthalmic Society meeting in 1989 [2] .…”